Synthesis of bioceramic compositions

ABSTRACT

A process for the synthesis of a bioceramic composition comprising calcium phosphosilicate (CPS, Ca 10 (PO 4 ) 4 (SiO 4 ) 2 ), the process comprising: providing calcium or a calcium-containing compound, a phosphorus-containing compound and a silicon-containing compound; and forming a precipitate by reacting the compounds in an aqueous phase at an alkali pH.

The present invention relates to biomedical materials and, inparticular, to calcium phosphate based bioceramics.

The combined effects of an ageing population and greater expectations inthe quality of life have resulted in an increasing global demand fororthopaedic implants for the replacement or augmentation of damagedbones and joints. In bone grafting current gold standards include theuse of autograft and allograft but these methods are increasinglyrecognised as non-ideal due to limitations in supply and consistency.Ceramics have been considered for use as bone graft substitutes toreplace or extend traditional bone grafts for over 30 years. Inparticular, calcium phosphates such as hydroxyapatite have been promotedas a result of their osteoinductive properties.

Accordingly, as surgical technique and medical knowledge continue toadvance, there has been a growth in the demand for synthetic bonereplacement materials. Consequently, there is an increasing interest inthe development of synthetic bone replacement materials for the fillingof both load bearing and non-load bearing osseous defects, such as injoint and facial reconstruction.

The biocompatibility of hydroxyapatite, coupled with the similaritiesbetween the crystal structure of hydroxyapatite and the mineral contentof bone, has led to great interest in hydroxyapatite as a material forthe augmentation of osseous defects. The apatite group of minerals isbased on calcium phosphate, with stoichiometric hydroxyapatite having amolar ratio of Ca/P of 1.67. Hydroxyapatite has the chemical formulaCa₁₀(PO₄)₆ (OH)₂.

Silicate (or silicon) substituted hydroxyapatite compositions provideattractive alternatives to stoichiometric hydroxyapatite as a bonereplacement material, as the presence of silicate ions in thehydroxyapatite lattice appears to enhance bone cell behaviour, andaccelerate bone repair. The substitution of silicate (or silicon) intothe hydroxyapatite does have a compositional limit; when the level ofsilicate substitution passes this limit, the hydroxyapatite becomesthermally unstable at typical sintering temperatures of about 1200° C.,and secondary phases such as tricalcium phosphate are formed. Thesubstitution limit for silicate substitution into the hydroxyapatitelattice is approximately 5.3 wt % (or 1.6 wt % silicon). PCT/GB97/02325describes a substituted hydroxyapatite material.

For the avoidance of doubt, the term silicate-substituted as used hereinalso encompasses silicon-substituted. Likewise, silicon-substituted asused herein also encompasses silicate-substituted.

Silicate substitution in hydroxyapatite can be described by thecomposition:

Ca₁₀(PO₄)_(6-x)(SiO₄)_(x)(OH)_(2-x)

The actual compositions that remain as a single, purehydroxyapatite-like phase upon sintering, such that they form ceramics,are limited to a value of approximately x=0.6. For higher values of x,multiphase compositions are obtained.

When x=2.0, the composition is described as:

Ca₁₀(PO₄)₄(SiO₄)₂

This specific phase is described as calcium silico-phosphate (termedCPS), or by the mineral name silicocarnotite. The structure of thismaterial, prepared by a solid state method, was reported by Dickens etal (B. Dickens, W. E. Brown, “Crystal structure of silicocarnotite”,Tschermakis Mineral Petrogr Mitt 1971; 16: 1-27). A more recentsynthesis, using hydrothermal synthesis, was described by Balas et al,where they used the final product as an X-ray Photoelectron Spectroscopy(XPS) reference material (F. Balas et al, “In vitro bioactivity ofsilicon-substituted hydroxyapatite”, J. Biomed. Mater. Res. 66A (2003)364-375). Kim et al observed the formation of a CPS phase in asilicon-substituted hydroxyapatite composition containing 3.76 wt % Si(corresponding to x=1.3 in Ca₁₀(PO₄)_(6-x)(SiO₄)_(x)OH_(2-x)) (S. R. Kimet al, “Synthesis of Si,Mg-substituted hydroxyapatites and theirsintering behaviour”, Biomaterials 24 (2003) 1389-1398). The maximumamount of CPS phase formed, however, was less that 30%.

H-W. Lee and J-H Kim, Korean Ceramic Academy Society 31 (1994)“Properties of Hydration and Strength of Sol-gel derived fine particlesin the system CaO—P₂O₅—SiO₂”; M. W. Barnes et al, “Hydration in thesystem Ca₂SiO₄—Ca₃(PO₄)₂ at 90° C.”, J. Am. Ceram Soc. 75[6] (1992)1423-1429. describe the formation of a calcium silico-phosphate, orsilicocarnotite, phase with hydraulic bone cement systems, which are lowtemperature reaction systems.

U.S. Pat. No. 4,612,053 relates to combinations of sparingly solublecalcium phosphates as remineralizers of caries lesions in dental enameland partially demineralized dentin and cementum and in their applicationas dental cements.

JP 3023245 and JP 3033059 relate to a low-cost hydraulic cementcompositions.

U.S. Pat. No. 6,342,547 relates to an epoxy resin composition for anSF₆-gas insulating device which is obtained by adding a silicatecompound powder to an epoxy resin.

JP 4022003 and JP 4022004 relate to an electric insulating member withhigh heat resistance and high electric insulating characteristics andwhich is composed of a complex of inorganic fibers and a curing hydrateof a calcium phosphate compound.

The present invention describes the synthesis, using an aqueousprecipitation reaction, of a composition that, on controlledsintering/heat-treatment, contains calcium silico-phosphate, orsilicocarnotite (and termed CPS), as the major phase, for use as abioceramic implant material.

This synthesis reaction, and subsequent heat-treatment is suitable toproduce industrial scale quantities of this bioceramic composition.

Accordingly, in a first aspect, the present invention provides a processfor the synthesis of a bioceramic composition comprising calciumphosphosilicate (CPS, Ca₁₀(PO₄)₄(SiO₄)₂), the process comprising:

-   -   providing calcium or a calcium-containing compound, a        phosphorus-containing compound and a silicon-containing        compound; and    -   forming a precipitate by reacting the compounds in an aqueous        phase at an alkali pH.

The process may be used to produce a composition as herein describedwith reference to any of the other aspects according to the presentinvention.

The present invention will now be further described. In the followingpassages different aspects of the invention are defined in more detail.Each aspect so defined may be combined with any other aspect or aspectsunless clearly indicated to the contrary. In particular, any featureindicated as being preferred or advantageous may be combined with anyother feature or features indicated as being preferred or advantageous.

The calcium phosphosilicate (CPS) is preferably present in thecomposition as the predominant phase and is preferably present in anamount of 50 wt. % or more, more preferably 60 wt. % or more, still morepreferably 70 wt. % or more, still more preferably 80 wt. % or more.

The inventors have found that in order to obtain a high yield of CPS,the molar ratio of calcium to phosphate+silicate is advantageouslychosen to be about 10:6. For the same reason, the molar ratio ofphosphate to silicate is advantageously chosen to be from about 5:1 toabout 4:2. In a preferred embodiment, the molar ratio of phosphate tosilicate is from about 4.2:1.8 to about 4:2, relative to 10 moles ofcalcium.

The calcium-containing compound is preferably a calcium salt and may,for example, be selected from one or more of calcium hydroxide, calciumchloride, calcium nitrate and/or calcium nitrate hydrate.

The phosphorus-containing compound is preferably selected from one orboth of a phosphate salt and/or a phosphoric acid, more preferably fromone or both of ammonium phosphate and/or phosphoric acid.

The silicon-containing compound is preferably a silicate and may, forexample, be selected from one or both of tetraethyl orthosilicate (TEOS)and/or silicon acetate.

The silicate is preferably present in the material in an amount of up to20 weight percent, more preferably from 12 and 20 weight percent, stillmore preferably from 17 and 20 weight percent.

The aqueous precipitation step or steps are preferably carried out at analkali pH. In order to optimise the yield of CPS, the inventors havefound that the pH is preferably from 8 to 13, more preferably from 10 to12.

An alkali may be added to adjust the pH of the solution to the desiredpH. A suitable example is ammonium hydroxide.

The aqueous precipitation method according to the present invention maybe carried out at room temperature (typically from 20 to 30° C.)

After the precipitate has been formed it is preferably heated to atemperature in the range of from 1000° C. to 1600° C., more preferablyfrom 1100° C. to 1500° C., still more preferably from 1200° C. to 1300°C. The material is preferably sintered at these temperatures. Theinventors have found that sintering within these temperature rangesincreases the yield of CPS.

The precipitate is preferably heated for a periods of from 1 to 120hours, more preferably from 2 to 32 hours, still more preferably from 4to 16 hours. This preferred heating time is significantly longer thanconventional times used to sinter hydroxyapatite or silicate-substitutedhydroxyapatite ceramics, as long sintering times of greater than 1-2hours lead to an increase in grain size of the ceramics, a reduction instrength and an increase in manufacturing costs. However, in the case ofthe present invention, the inventors have found that prolongedsintering/heating times of at least 2 hours leads to the formation ofgreater quantities of the CPS phase, at the expense of ahydroxyapatite-like phase and an alpha-tricalcium phosphate-like phase.The heating step will typically result in sintering of the material.

The process may further comprise cooling the sample from the heatingtemperature and optionally carrying out a post-heating annealing step.These additional steps are useful because they facilitate thetransformation of any alpha-tricalcium phosphate secondary phase to abeta-tricalcium phosphate if desired.

The bioceramic composition may also contain an amorphous phase as aminor component (typically less than 2 wt. %). The bioceramiccomposition may also contain unavoidable impurities (typically less than1 wt. %).

In a second aspect, the present invention provides a syntheticbioceramic composition comprising calcium phosphosilicate (CPS,Ca₁₀(PO₄)₄(SiO₄)₂), the composition being obtained by a processcomprising:

-   -   an aqueous precipitation step or steps involving mixing calcium        or a calcium-containing compound, a phosphorus-containing        compound and a silicon-containing compound; and    -   heating the collected product produced by the aqueous        precipitation step or steps.

In one embodiment, the synthetic bioceramic composition comprisescalcium phosphosilicate as the predominant phase together with one ormore secondary, minor phases such as, for example, hydroxyapatite,silicate-substituted hydroxyapatite, alpha-tricalcium phosphate,beta-tricalcium phosphate, brushite, monetite, tetracalcium phosphate,octacalcium phosphate, calcium pyrophosphate, calcium silicate, calciumoxide, calcium carbonate, amorphous calcium phosphate glass, amorphouscalcium silicate glass, and/or amorphous calcium phospho-silicate glass.

The calcium phosphosilicate phase may constitute from 50 to 98 wt. % ofthe total crystalline phase composition, preferably from 70 to 98%, morepreferably from 90 to 98%. The remainder of the composition may, forexample, be composed of one or more of the secondary, minor phases asdescribed above. Accordingly, the synthetic bioceramic composition maycontain, for example, from 2 to 30 wt. % of one or more of thesesecondary, minor phases. The preferred minor phases comprise one or moreof hydroxyapatite, silicate-substituted hydroxyapatite, alpha-tricalciumphosphate and/or beta-tricalcium phosphate. The presence of theabove-described secondary phases may be desirable because they affectthe rate at which calcium and phosphate ions become available in vivo.

In one preferred embodiment, the calcium phosphosilicate phaseconstitutes approximately 98 (±2) wt. % of the total crystalline phasecomposition.

In another preferred embodiment of the present invention, there isprovided a synthetic bioceramic composition comprising calciumphosphosilicate (CPS) as the predominant phase, wherein the secondaryphase comprises hydroxyapatite and/or a hydroxyapatite-like phase.Hydroxyapatite-like phase is intended to encompass, for example,silicate-substituted hydroxyapatite. The calcium phosphosilicate mayconstitute 70 to 98 wt. % of the composition, more preferably 80 to 98wt. %. The secondary phase may constitute from 2 to 30 wt. % of thecomposition, more preferably 2 to 20 wt. %. Small amounts (typically <1wt. %) of unavoidable impurities may also be present.

In another preferred embodiment of the present invention, there isprovided a synthetic bioceramic composition comprising calciumphosphosilicate (CPS) as the predominant phase, wherein the secondaryphase comprises one or more of alpha-tricalcium phosphate, analpha-tricalcium phosphate-like phase, beta-tricalcium phosphate and/ora beta-tricalcium phosphate-like phase. The calcium phosphosilicate mayconstitute 70 to 98 wt. % of the composition, more preferably 80 to 98wt. %. The secondary phase may constitute from 2 to 30 wt. % of thecomposition, more preferably 2 to 20 wt. %. Small amounts (typically <1wt. %) of unavoidable impurities may also be present.

In another preferred embodiment of the present invention, there isprovided a synthetic bioceramic composition comprising calciumphosphosilicate (CPS) as the predominant phase, wherein the secondaryphase comprises: (i) hydroxyapatite and/or a hydroxyapatite-like phase;and one or both of (ii) alpha-tricalcium phosphate and/oralpha-tricalcium phosphate-like phase; and/or (iii) beta-tricalciumphosphate and/or beta-tricalcium phosphate-like phase. The calciumphosphosilicate may constitute 70 to 98 wt. % of the composition, morepreferably 80 to 98 wt. %. The secondary phase may constitute from 2 to30 wt. % of the composition, more preferably 2 to 20 wt. %. Smallamounts (typically <1 wt. %) of unavoidable impurities may also bepresent.

As noted above, the presence of the above-described secondary phases maybe desirable because they affect the rate at which calcium and phosphateions become available in vivo. For example, alpha-tricalcium phosphateis more soluble than CPS and will therefore render calcium and phosphateions more quickly.

The present invention also provides for a synthetic bone material, boneimplant, orthopaedic implant, tissue implant, bone graft, bonesubstitute, bone scaffold, filler, coating or cement comprising acomposition as herein described. The present invention also provides forthe use of the compositions as herein described in these applications.The present invention also provides for a method of treating a patient,the method comprising delivering a bioceramic composition as hereindescribed to a site in the patient to be treated. The present inventionalso provides a bioceramic composition as herein described for use as abiomedical implant. The present invention also provides a bioceramiccomposition as herein described for use in therapy. The presentinvention also provides a bioceramic composition as herein described foruse in reconstructive or replacement surgery.

It will be appreciated that bioceramic composition as herein describedmay be used in these biomedical applications on its own or inconjunction with one or more of a biocompatible polymer, other type ofceramic, glass, and/or glass-ceramic material.

The present invention will now be described further, by way of example,with reference to the following non-limiting examples and theaccompanying drawings in which:

FIG. 1 is an X-ray diffraction pattern of the calcium silicophosphatecomposition CPS-1.8 (x=1.8, pH 12) sintered at 1300° C. for 8 hours(arrow indicates alpha-TCP as a minor second phase, with all other peakscorresponding to CPS phase);

FIG. 2 is a Fourier Transform Infra-red (FTIR) spectrum, obtained usinga PAS cell, of the calcium silicophosphate composition CPS-1.8 (x=1.8,pH 12) sintered at 1300° C. for 8 hours.

FIG. 3 shows the effect of sintering time on the phase composition ofthe calcium silicophosphate composition CPS-2.0 (x=2.0, pH 12) sinteredat 1200° C.

FIG. 4 is an X-ray diffraction pattern of the calcium silicophosphatecomposition CPS-2.0 (x=2.0, pH 12) sintered at 1300° C. for 8 hours(arrow indicates alpha-TCP as a minor second phase, with all other peakscorresponding to CPS phase).

EXAMPLE 1 Synthesis of a Bioceramic with Calcium Silicophosphate (CPS)as the Main Phase (x=1.8)

The starting materials for the synthesis were as described in Table 1.

TABLE 1 Starting reagents used to synthesise a bioceramic with CalciumSilicophosphate (CPS) as the main phase. CaCO₃ (99+% Sigma-Aldrich)H₃PO₄ (85 wt % Sigma-Aldrich) TEOS (98% Sigma Aldrich)

Small batches of the novel materials of approximately 10 grams wereprepared. Calcium carbonate powder was decarbonated for 24 hours priorto synthesis to produce calcium oxide, by placing the powder in a silicacrucible and heating at 900° C. in a furnace. The calcium oxide powderwas added to 200 mL of distilled water to form a hydrated calciumhydroxide solution. Prepared solutions of orthophosphoric acid andtetraethylorthosilicate (TEOS) were then added (together) drop wise withcontinuous stirring. In a similar synthesis, the orthophosphoric acidand tetraethylorthosilicate solutions were added separately. The pH wasadjusted to the required level during the addition of the H₃PO₄/TEOSsolution by the addition of a suitable base, such as ammonia solution,sodium hydroxide or potassium hydroxide. The precipitate was thencovered and stirred for a further hour before leaving to standovernight. The precipitate was then filtered using a Buchner funnel andvacuum pump. It was removed from the funnel and allowed to dry in adrying oven at around 80° C. for 24 hours.

The following equation represents the formula for calciumsilicophosphate (CPS):

Ca₁₀(PO₄)_(6-x)(SiO₄)_(x)(OH)_(2-x)

where x is equal to the level of doping.

A range of compositions were prepared with values of x ranging from 1.4to 2.4. It was found that the optimum range in terms of CPS yield wasbetween 1.6 and 2.2, and most preferably 1.8-2.0.

For x=2.0, the formula becomes Ca₁₀(PO₄)₄(SiO₄)₂, equivalent toCa₅(PO₄)₂(SiO₄), the reported CPS phase which contains no hydroxylgroups. The x values were calculated as outlined in the example below.

For x=1.8 (CPS-1.8) the following equation can be written:

10CaO+4.2H₃PO₄+1.8Si(OC₂H₅)₄→Ca₁₀(PO₄)_(4.2)(SiO₄)_(1.8)(OH)_(0.2)

The above equation is true, provided that synthesis pH is ≧8.

Divide by a factor of 100 (because only 10 g is required) to give:

-   -   0.1 moles of CaO=5.6079 g    -   0.042 moles of H₃PO₄=4.842 g (adjusted to compensate for 85 wt %        starting material)    -   0.018 moles of TEOS=3.750 g

When synthesising larger batches, for example 50 g, the dividing factoris reduced to 20 to give the masses of reactants required.

The synthesis for each x value was repeated 3 times but at pH values of8, 10 and 12. The pH was monitored during the synthesis using a pHmeter. The pH was adjusted using ammonia solution and nitric acid asrequired. The pH was monitored until most of the orthophosphoricacid/TEOS solution had been added, and was then adjusted accordinglyuntil the synthesis was complete. It has been found that an alkali pH offrom 8 to 12 provides a good yield of CPS.

The synthesis of the samples at all x values and all pHs was repeated,but with the addition of orthophosphoric acid being made before theaddition of TEOS. It was decided not to use this method for the mainsyntheses as it is possible that after addition of orthophosphoric acid,the stoichiometric HA may form preferentially and impede the inclusionof silicate. By adding the two solutions together (the preferred method)it is believed that the intended stoichiometry (Si/P) would remain.

All filtered and dried samples were sintered as powders in platinumboats in a furnace. The temperature was raised by 5° C. per minute untilthe target temperature was reached. The temperature was then held atthis temperature for a given period of time before cooling to 25° C. ata rate of 10° C. per minute.

Sintering was carried out at 1100, 1200 and 1300° C. for times of 2, 4,8 and 16 hours in order to monitor the development of phase compositionsunder these different conditions.

Samples underwent phase characterisation using an X-ray diffractometerwith Cu Kα radiation, λ=1.5418 Å. Phase analysis was carried out on eachsample to determine the phase composition of the sintered sample. Thiswas done using EVA software and standard patterns from the powderdiffraction file.

To calculate the percentage compositions of the samples a commercialquantitative phase analysis technique was used (TOPAS), which determinedthe relative amounts of the crystalline phases present from the X-raydiffraction data.

For a sample with x=1.8 (CPS-1.8), prepared at pH=12, and sintered at1300° C. for 8 hours, the major phase was calcium silicophosphate (CPS),with alpha-tricalcium phosphate present as a minor phase; the phasecomposition determined from quantitative phase analysis of the X-raydiffraction data is listed in Table 2.

TABLE 2 The phase composition determined from quantitative phaseanalysis of a composition with x = 1.8, pH = 12, sintered at 1300° C.for 8 hours (CPS-1.8). Calcium silicophosphate 89% (CPS)alpha-tricalcium phosphate 11%

Chemical analysis of this composition was performed using XRF and theresults are listed in Table 3. The Ca/(P+Si) molar ratio is slightlyless than the designed composition of 1.67, and this is consistent withthe small amount of a-TCP observed by X-ray diffraction.

TABLE 3 Chemical compositions, determined from XRF analysis, of acomposition with x = 1.8, pH = 10, sintered at 1300° C. for 8 hours(CPS-1.8). CaO (wt %) 57.64% P2O5 (wt %) 31.92% SiO2 (wt %)  10.5% Si(wt %) 4.9 Ca/(P + Si) 1.65

The final composition described in Table 2 was designed to have calciumsilicophosphate (CPS) as the major phase, with the biologically activealpha-tricalcium phosphate being present as a minor phase. The presenceof this well-characterised calcium phosphate phase as minor second phaseenhances the biological behaviour of this bioceramic composition incertain applications.

The X-ray diffraction pattern of the composition with x=1.8, pH=12,sintered at 1300° C. for 8 hours (CPS-1.8) is shown in FIG. 1, and thecorresponding Fourier Transform Infrared (FTIR) spectrum is shown inFIG. 2.

The effect of increasing the sintering time from 2 to 16 hours on thephase composition of samples sintered at 1200° C. is shown in FIG. 3.Increasing the sintering time resulted in a decrease in the amount of ahydroxyapatite-like phase and a surprisingly large increase in theamount of CPS phase, such that after 2 hours it is present in equalproportions to the hydroxyapatite-like phase, whereas after 8 or 16hours the CPS phase is the predominant phase. By contrast, sintering asingle phase hydroxyapatite or a silicate-substituted hydroxyapatitesamples would not result in any change in phase composition withprolonged sintering/heating time at 1200° C.

The FTIR spectra shows characteristic peaks corresponding to phosphateand silicate groups, and the absence of any significant peakcorresponding to hydroxyl groups at ˜3570 cm−1, showing that thiscomposition contains predominantly the calcium silicophosphate (CPS)phase.

The effect of soaking the composition with x=1.8, pH=12, sintered at1300° C. for 8 hours (CPS-1.8) in a TRIS-buffer at pH 7.4 and 37° C. for120 hours, as described by ISO 10993-14 showed that the pH of thesoaking solution increase from 7.4 to 7.95 (SD=0.03), whereas asingle-phase hydroxyapatite samples showed only a small increase in pHfrom 7.4 to 7.58 (SD=0.02) over the same soaking period. The weight lossof the samples with composition with x=1.8, pH-12, sintered at 1300° C.for 8 hours (CPS-1.8) was 2.21% (SD=0.33), whereas the single-phasehydroxyapatite samples showed a larger decrease in weight of 4.95%(SD-0.33) over the same time period. The sample with composition CPS-1.8actually showed evidence by scanning electron microscopy (SEM) of theprecipitation of a calcium phosphate apatite-like phase on the surfaceof the soaked granules, which is consistent with the decrease in samplemass (dissolution of Ca and PO4 ions into solution) and the increase inpH (which favours the precipitation of a surface apatite-like layer).The single-phase hydroxyapatite samples did not show any evidence by SEMof the precipitation of an apatite-like phase on the surface of thesamples.

EXAMPLE 2 Synthesis of a Bioceramic with Calcium Silicophosphate (CPS)as the Main Phase (x=2.0)

For x=2.0 (CPS-2.0) the following equation can be written:

10CaO+4H₃PO₄+2Si(OC₂H₅)₄→Ca₁₀(PO₄)₄(SiO₄)₂

The above equation is true, provided that synthesis pH is 8.

Divide by a factor of 100 (because only 10 g is required) to give:

-   -   0.1 moles of CaO=5.6079 g    -   0.04 moles of H₃PO₄=4.842 g (adjusted to compensate for 85 wt %        starting material)    -   0.02 moles of TEOS=3.750 g

When synthesising larger batches, for example 50 g, the dividing factoris reduced to 20 to give the masses of reactants required.

The synthesis and characterisation of samples with x=2.0 were performedas described in Example 1, for x=1.8.

The phase composition of sample CPS-2.0 after sintering at 1300° C. for8 hours, determined by quantitative phase analysis of the X-raydiffraction data, is listed in Table 4. The composition consists ofcalcium silicophosphate as the predominant phase, with a small amount ofalpha-TCP as a second phase; the amount of alpha-TCP in the CPS-2.0sample was less than considerably less than that observed in the CPS-1.8sample (11%, Table 2).

TABLE 4 The phase composition determined from quantitative phaseanalysis of a composition with x = 2.0, pH = 12, sintered at 1300° C.for 8 hours (CPS-2.0). Calcium silicophosphate 98% (CPS)alpha-tricalcium phosphate  2%

Chemical analysis of this composition was performed using XRF and theresults are listed in Table 5. The amount of Si incorporated is greaterthan observed for composition x=1.8, as would be expected. Again, theCa/(P+Si) molar ratio is slightly less than the designed composition of1.67, and this is consistent with the small amount of a-TCP observed byX-ray diffraction.

TABLE 5 Chemical compositions, determined from XRF analysis, of acomposition with x = 2.0, pH = 12, sintered at 1300° C. for 8 hours(CPS-2.0). CaO (wt %) 57.78% P2O5 (wt %) 30.65% SiO2 (wt %)  11.7% Si(wt %) 5.5 Ca/(P + Si) 1.64

The X-ray diffraction pattern of sample CPS-2.0, sintered at 1300° C.for 8 hours, is shown in FIG. 4.

1-20. (canceled)
 21. A synthetic bioceramic composition comprisingcalcium phosphosilicate (CPS, Ca₁₀(PO₄)₄(SiO₄)₂).
 22. A syntheticbioceramic composition according to claim 21 and comprising calciumphosphosilicate as the predominant phase.
 23. A synthetic bioceramiccomposition according to claim 21 and comprising calcium phosphosilicateas the predominant phase, wherein the secondary, minor phases includeone or more of hydroxyapatite, silicate-substituted hydroxyapatite,alpha-tricalcium phosphate, beta-tricalcium phosphate, brushite,monetite, tetracalcium phosphate, octacalcium phosphate, calciumpyrophosphate, calcium silicate, calcium oxide, calcium carbonate,amorphous calcium phosphate glass, amorphous calcium silicate glass,and/or amorphous calcium phospho-silicate glass.
 24. A syntheticbioceramic composition according to claim 21, wherein the calciumphosphosilicate phase constitutes approximately 98 (±2) wt. % of thetotal crystalline phase composition.
 25. A synthetic bioceramiccomposition according to claim 21, wherein the calcium phosphosilicatephase constitutes from 50 to 98 wt. % of the total crystalline phasecomposition.
 26. A synthetic bioceramic composition according to claim21, which also contains an amorphous phase as a minor component.
 27. Asynthetic bone material, bone implant, bone graft, bone substitute, bonescaffold, filler, coating or cement comprising a composition as definedin claim
 21. 28-29. (canceled)
 30. A synthetic bioceramic compositioncomprising of calcium phosphosilicate (CPS, Ca₁₀(PO₄)₄(SiO₄)₂) as thepredominant phase, wherein the secondary phase (s) comprise (s): (i)hydroxyapatite and/or a hydroxyapatite-like phase; and one or both of(ii) alpha-tricalcium phosphate and/or alpha-tricalcium phosphate-likephase; and/or (iii) beta-tricalcium phosphate and/or beta-tricalciumphosphate-like phase.
 31. A synthetic bone material, bone implant, bonegraft, bone substitute, bone scaffold, filler, coating or cementcomprising a composition as defined in claim 30.